The present invention relates to monoclonal antibodies specific for a cell receptor that binds human stem cell factor (hSCF), as well as pharmaceutical compositions containing such monoclonal antibodies and uses of such monoclonal antibodies.
Stem Cell Factor (SCF) is a growth factor that stimulates the proliferation of pluripotent hematopoietic progenitor cells. It has been produced recombinantly in E. coli and various mammalian cells Zsebo et al., Cell 63:195-212 (1990); and co-pending U.S. patent applications Ser. Nos. 07/589,701, 07/573,616, and 07/537,198, filed Oct. 1, 1990, Aug. 24, 1990, and Jun. 11, 1990, respectively !.
The proto-oncogene c-kit has recently been identified as the receptor for SCF Zsebo et al., Cell 63: 213-224 (1990)!. Prior to identification of c-kit as the ligand for SCF, the c-kit receptor was known to exist Yarden et al., EMBO J. 6: 3341-3351 (1987); Qiu et al., EMBO J. 7: 1003-1011 (1988); Flanagan and Leder, Cell 63: 185-194 (1990)!.
Polyclonal antibodies directed against the murine c-kit have been reported Cellular Biology 8: 4896-4903 (1988)!, but it is not known whether these antibodies will cross react with the human c-kit, whether they will block binding of SCF to its receptor, or whether they will affect cell growth. A polyclonal antibody raised against a human c-kit carboxy terminal peptide has also been reported EMBO J. 6: 3341-3351 (1987)!, but these antibodies would not block SCF binding to the receptor. A monoclonal antibody that recognizes human SCF receptors has been reported Lerner et al., Blood 76 (Suppl):295a, (1990); Ashman et al., Leukemia Res. 12: 923-928 (1988); Cambaseri et al., Leukemia Res. 12: 929-939 (1988); Gadd and Ashman, Leukemia Res. 11: 1329-1336 (1985)!.
Thus, until the existence of the present invention, the prior art has not been able to obtain a monoclonal antibody to the c-kit receptor with any expectation that such a monoclonal antibody would possess the ability to block the binding of the c-kit ligand, SCF.
This research is partially funded by the United Sates Government through National Institute of Health Grant P01-DK-31232 and the American Cancer Society Grant JFRA217.